{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:18:02Z","timestamp":1784647082912,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures","award":["171\/11\/09.01.2024"],"award-info":[{"award-number":["171\/11\/09.01.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastric cancer remains a major global health burden, with limited response rates to current immunotherapies targeting the programmed death-ligand 1 (PD-1\/PD-L1) axis. Recent studies have identified sialic acid-binding immunoglobulin-like lectin 15 (SIGLEC-15) as a novel immune checkpoint molecule that may drive immune evasion through PD-L1\u2013independent pathways. This study aimed to evaluate the expression patterns of SIGLEC-15 and PD-L1 in gastric adenocarcinoma and to investigate their associations with clinicopathological features and patient outcomes. We retrospectively analyzed 133 consecutive cases of gastric adenocarcinoma with complete clinicopathologic and follow-up data. Immunohistochemical staining was performed on formalin-fixed tumor samples; SIGLEC-15 expression on tumor cells was quantified by H-score (high expression defined as \u2265110) and PD-L1 status by combined positive score (CPS, positive if \u22651). High SIGLEC-15 expression correlated with multiple adverse pathological features, including lymphatic (p = 0.003), venous (p = 0.030), and perineural invasion (p = 0.010), and was associated with significantly poorer 3-year overall survival (hazard ratio = 3.36, p &lt; 0.001). While SIGLEC-15 and PD-L1 expression were not mutually exclusive, an inverse relationship was generally observed. Patients with dual positivity (SIGLEC-15 high\/PD-L1 CPS \u2265 1) showed the lowest 36-month survival (32%), compared to 56% in the dual-negative group (SIGLEC-15 low\/PD-L1 CPS &lt; 1). These results highlight the clinical relevance of SIGLEC-15 as an independent marker of tumor aggressiveness and poor prognosis in gastric adenocarcinoma. Moreover, stratification based on combined SIGLEC-15 and PD-L1 CPS expression revealed that patients co-expressing high levels of both markers experienced the poorest survival outcomes. These findings suggest that the dual assessment of SIGLEC-15 and PD-L1 may enhance prognostic accuracy and support immunotherapeutic decision-making in gastric cancer.<\/jats:p>","DOI":"10.3390\/ijms26178637","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:51:21Z","timestamp":1757065881000},"page":"8637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive Analysis of SIGLEC-15 and PD-L1 Expression Identifies Distinct Prognostic Profiles in Gastric Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Andreea-Raluca","family":"Cozac-Sz\u0151ke","sequence":"first","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-6256","authenticated-orcid":false,"given":"Andreea C\u0103t\u0103lina","family":"Tinca","sequence":"additional","affiliation":[{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-6576","authenticated-orcid":false,"given":"Anca","family":"Negovan","sequence":"additional","affiliation":[{"name":"Department of Clinical Science-Internal Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Vilaia","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases I, Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-7263","authenticated-orcid":false,"given":"Dan-Alexandru","family":"Cozac","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-2433","authenticated-orcid":false,"given":"Iuliu-Gabriel","family":"Cocuz","sequence":"additional","affiliation":[{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Hora\u021biu","family":"Sab\u0103u","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca-Diana","family":"Hag\u0103u","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana-Maria","family":"Chiorean","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea-Bianca","family":"Lazar","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7085-4755","authenticated-orcid":false,"given":"Sabin","family":"Turdean","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-5959","authenticated-orcid":false,"given":"Em\u0151ke-Andrea","family":"Sz\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Histology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3734-5305","authenticated-orcid":false,"given":"Alexandru Nicu\u0219or","family":"Tomu\u021b","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidiu Simion","family":"Cotoi","sequence":"additional","affiliation":[{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6578273","DOI":"10.1155\/2018\/6578273","article-title":"Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer","volume":"2018","author":"Pavlovic","year":"2018","journal-title":"Gastroenterol. 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